T-cell chronic lymphocytic leukemia. Unusual morphologic, phenotypic, and karyotypic features in association with light chain amyloidosis.

BACKGROUND: Lymphocytes that display a phenotype of mature B-cells, T-cells, natural killer (NK) cells, or a combination of T-cells and NK cells can be found in patients with lymphoproliferations that manifest as expansions of peripheral blood lymphocytes (PBL). If these PBL expansions exhibit clonality, they can be classified as chronic lymphocytic leukemia (CLL). METHODS/RESULTS: A patient who had two simultaneous, clonal lymphoproliferative disorders manifested as an unusual T-cell CLL in conjunction with systemic light chain amyloidosis is described. Gene rearrangement studies of the PBL of the patient showed clonal rearrangements of both the T-cell receptor beta (T beta) chain and the immunoglobulin genes. Additional immunologic and microscopic studies of the T-cells of the patient showed that they were large, agranular, CD4+ T-cells that also expressed the NK cell marker CD57. Cytogenetics disclosed an unusual karyotype in the PBL. CONCLUSIONS: The pathogenesis of this T-cell CLL and whether it truly represents a malignant disorder, as well as its relation to amyloidosis, is discussed.

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells.

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.

HIV-associated Hodgkin disease: a clinical study of 18 cases and review of the literature.

Intermediate- and high-grade B-cell non-Hodgkin lymphoma (NHL) occurring in a human immunodeficiency virus (HIV)-infected patient is considered diagnostic of the acquired immunodeficiency syndrome (AIDS). Other neoplasms (both hematopoietic and nonhematopoietic) have also been reported in patients with HIV infection, although none except Kaposi sarcoma carries the same diagnosis of AIDS as B-cell NHL in an HIV-infected host. There have been previous reports in the literature of Hodgkin disease (HD) in HIV-infected patients. We describe our clinical and pathological experience with HD from 1984-1989, in 18 patients with documented HIV infection and also review the literature on HD in HIV-infected patients. Almost all patients described herein presented with advanced disease and mixed cellularity histology and did very poorly despite some good initial responses to therapy. By statistical analysis, we found that the patients with HIV-associated HD had a strong tendency to be outside the age range seen in non-HIV-associated HD (P less than 0.005). We also discuss the possible relationship between HIV and HD and consider whether HIV-associated HD, like B-cell NHL, is a manifestation of AIDS.

Angiocentric immunoproliferative lesion/T-cell non-Hodgkin's lymphoma and the acquired immune deficiency syndrome: a case report and review of the literature.

The lesions known as lymphocytic vasculitis, polymorphic reticulosis (midline malignant reticulosis, lethal midline granuloma), lymphomatoid granulomatosis, and angiocentric lymphoma form what have been collectively termed the angiocentric immunoproliferative lesions (AIL). Because of recent reports demonstrating clonal rearrangements of the T-cell receptor in these lesions, the AIL are now thought to represent a continuous spectrum of post-thymic T-cell non-Hodgkin's lymphoma (NHL). NHL associated with the acquired immune deficiency syndrome (AIDS) represents intermediate or high-grade B-cell malignancies in HIV-infected patients that may be etiologically related to the Epstein-Barr virus (EBV). There have been reports of EBV-associated T-cell NHL, AIL, and large granular lymphocyte (LGL) proliferations, as well as HIV-associated T-cell neoplasia, LGL/T-cell proliferations, and AIL. We describe a case of polymorphic reticulosis (lethal midline granuloma) arising in an HIV-infected individual, who later progressed to AIDS, and review the literature on HIV-associated and EBV-associated T-cell neoplasia, LGL/T-cell proliferations, and AIL. The etiology of this AIL/T-cell NHL, especially in relation to EBV and HIV, is discussed.

Malignant plasma cell tumors in human immunodeficiency virus-infected patients.

The development of malignant neoplasms in patients with the acquired immune deficiency syndrome (AIDS) or with a positive human immunodeficiency virus (HIV) antibody test is a well known phenomenon. According to the guidelines from the Centers for Disease Control (Atlanta, GA), the presence of intermediate-grade or high-grade B-cell non-Hodgkin's lymphoma in HIV antibody-positive patients is considered a diagnostic criterion for AIDS. The authors describe two cases of malignant plasma cell tumors in two young HIV-infected patients. In light of this and other reports of plasma cell tumors in patients at risk for AIDS or with a positive HIV antibody test, the finding of another manifestation of B-cell neoplasia in these patients may enlarge the spectrum of AIDS-related tumors.

Recombinant human erythropoietin for patients with AIDS treated with zidovudine.

Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo-controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels less than or equal to 500 IU per liter at base line, but not in patients whose levels were greater than 500 IU per liter at the beginning of the study. Although the hematocrit and hemoglobin level were not used as the primary criteria of efficacy because the patients received transfusions when their physicians decided that they needed them, a significantly higher rate of increase in the hematocrit was observed in the patients treated with recombinant human erythropoietin whose levels of endogenous erythropoietin were less than or equal to 500 IU per liter (0.00353 points per week) than in the patients given placebo (0.00116 points per week). This effect was not seen in patients with higher levels of endogenous erythropoietin. Serious side effects did not occur more often in the group treated with erythropoietin than in the placebo group. We conclude that recombinant human erythropoietin may be useful in patients with AIDS treated with zidovudine, although the indicators for its use remain to be clarified.

B-cell acute lymphocytic leukemia in HIV-antibody-positive patients.

B-cell non-Hodgkin lymphoma (NHL) has been well described in association with human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS). Many of these lymphomas are of the diffuse, aggressive, subtype B-cell NHL, including Burkitt and Burkitt-like lymphoma. Recently, there have been reports of B-cell acute lymphocytic leukemia (ALL), Burkitt type, in patients who were either HIV antibody-positive or at high risk for AIDS. We have seen three cases of B-cell ALL, Burkitt type, and herein describe their clinical and laboratory characteristics. All patients were HIV antibody-positive. Since stage IV Burkitt lymphoma in blood phase and B-cell ALL, Burkitt type, represent a continuum of the same disease, and since it is also an aggressive B-cell malignancy, we suggest that B-cell ALL, Burkitt type, in HIV antibody-positive patients should support the diagnosis of AIDS.

Hybrid acute leukemia in an HIV-antibody-positive patient.

Although the great majority of acute leukemias have been designated as being of lymphocytic or myelocytic origin, recent reports have described elements of both in some patients. We describe here the first case of hybrid acute leukemia in an HIV-antibody-positive patient as well as the first hybrid involving B-cell (Burkitt) acute lymphocytic leukemia and acute myelomonocytic leukemia proven by cytochemical, immunologic, and cytogenetic methods. This case illustrates the increasingly complex difficulties in the diagnosis and treatment of AIDS-related malignancies.

Human immunodeficiency virus-related lymphoreticular malignancies and peripheral neurologic disease. A report of four cases.

The most common human immunodeficiency virus-related (HIV) malignancies to date include Kaposi's sarcoma and the high-grade non-Hodgkin's lymphomas. There also appears to be an association between HIV and an aggressive form of Hodgkin's disease. In addition, there is a spectrum of HIV-related central and peripheral neurologic syndromes. This article documents four patients with HIV-associated lymphoma who presented with peripheral neurologic syndromes as part of their neoplastic process. Autopsy results obtained from two of these patients showed direct nerve infiltration by lymphoma. All patients had an elevated serum lactate dehydrogenase (LDH). It is recommended that HIV-related lymphoma be considered in a high-risk patient who presents with a peripheral neurologic syndrome especially if there is an elevated serum LDH.

[Monotherapy of endemic Kaposi sarcoma with long-term vincristine infusion]. / Monotherapie des endemischen Kaposi-Sarkoms mit Vincristin-Dauerinfusion.

Twelve patients with endemic Kaposi's sarcoma (KS) were entered into a clinical trial of vincristine (VCR) infusion. Patients received 5-day courses of VCR, 0.25 mg/m2/day by continuous infusion, after an 0.5 mg intravenous bolus injection. Courses were repeated every four weeks. Stabilization of disease occurred in nine patients and could be maintained for a mean of 3 months (range: 2-7 months). Complete or partial remissions were not achieved with this protocol. Complications of therapy consisted of development of moderate neurotoxicity and paralytic ileus in one patient. Two patients developed opportunistic infections while on therapy. Hematologic toxicity, nausea or emesis did not occur. Single agent VCR by infusion is well tolerated by patients with the acquired immunodeficiency syndrome (AIDS) but appears to have only limited activity in the treatment of AIDS-related KS.

Isolated leukemia cutis--a case report.

A 67-year-old woman with acute myelomonocytic leukemia had a clinical course characterized by the initial appearance of leukemia cutis without bone marrow involvement. When marrow involvement subsequently occurred, induction chemotherapy cleared all manifestations of the illness. Shortly thereafter, while blood and bone marrow remained in remission, the skin lesions reappeared. The introduction of 6-thioguanine, as part of the maintenance treatment protocol, resulted in the rapid and permanent disappearance of the leukemic skin infiltrates.

Complex chromosomal abnormalities in a patient with lymphoid blast crisis of chronic myelogenous leukemia.

A 46-year-old Chinese man underwent lymphoid blast crisis (Ia+, CALLA+, TdT+) after 5 years of chronic phase, Philadelphia-chromosome positive chronic myelogenous leukemia. Chromosome analysis revealed a hyperdiploid karyotype, including two Philadelphia chromosomes--55,XY,t(9;22) (q34;q11), +2, +5, +5, +6, +10, +18, +19, +21, +del(22)(qll----qter)--in the majority of the leukemic blasts. The constellation of a lymphoid blast crisis and complex chromosomal abnormalities usually associated with myeloid blast crisis as well as the clinical data are discussed.

Light chain myeloma with meningeal and pleural involvement.

A 76-year-old woman with newly diagnosed lambda light chain myeloma was found to have involvement of the pleura and meninges. Direct immunofluorescence demonstrated the monoclonal nature of plasma cells found in the pleural fluid; morphologically similar cells were found in the cerebrospinal fluid and bone marrow. Immunoelectrophoresis revealed lambda light chains in the pleural fluid and cerebrospinal fluid, as well as in the serum and urine. Clinically apparent pleural involvement and meningeal involvement by myeloma are each rare events. This is believed to be the first report of both phenomena occurring simultaneously and the first known case of light chain myeloma involving the cerebrospinal fluid.

Acute nonlymphocytic leukemia following gastric adenocarcinoma treated by surgery alone. Evidence for etiologic heterogeneity of "secondary" leukemias.

The case of a 36-year-old Hispanic man who developed acute nonlymphocytic leukemia 18 months following gastric adenocarcinoma treated by surgery alone is presented. Cytogenetic analysis of the leukemic cells revealed numerical and structural chromosomal rearrangements including chromosomes 5 and 7 and immunologic characterization of the blasts revealed terminal deoxynucleotidyltransferase positivity with monocytoid features. This report suggests that not all cases of acute nonlymphocytic leukemia following chemotherapy and/or radiotherapy, which characteristically display similar cytogenetic and immunologic features, should be exclusively ascribed to the leukemogenic properties of anticancer treatment.

The bone marrow in AIDS. A histologic, hematologic, and microbiologic study.

During one year, 55 bone marrow biopsies from 49 patients with CDC-defined acquired immune deficiency syndrome (AIDS) were studied. Eighty-three percent were normocellular or hypercellular; 17% were hypocellular. Marrow plasma cells were increased in 83% of patients, most showing polyclonal hypergammaglobulinemia. Forty percent of patients showed peripheral neutropenia, 29% thrombocytopenia, and 79% lymphopenia with markedly reduced T4+ lymphocytes. Eighty-five percent of patients were anemic, with iron studies showing a pattern consistent with the anemia of chronic disease. Mycobacterium avium-intracellulare (MAI) grew from ten (20%) biopsies, four with granuloma and six without granuloma (five of these six also showed marrow hypocellularity). Small poorly formed granuloma (70-150 micron) were seen in eight (16%) patients (four AFB-culture positive, 4 negative). Three of four granuloma-positive, culture-negative cases eventually grew MAI from autopsy material. Five (10%) patients had lymphoplasmacytic aggregates; later, one developed lymphoma, another, markedly atypical lymphoid hyperplasia. Two additional patients showed marrow B-cell lymphomas. Of these findings, only marrow MAI meets the CDC definition of AIDS. However, in this series, small ill-defined granulomas, lymphoplasmacytic aggregates, and B-cell lymphomas also were found. The authors conclude that these latter findings, when seen in high-risk patients, particularly those with lymphopenia, anemia, and/or hypergammaglobulinemia, also strongly suggest the diagnosis of AIDS.

Autoimmune hyperthyroidism and thrombocytopenia developing in a patient with chronic lymphocytic leukemia.

A 56-year-old white man is described whose course of chronic lymphocytic leukemia (CLL) was complicated by the occurrence of the autoimmune hyperthyroidism/thrombocytopenia syndrome. The implications of this syndrome on the treatment of CLL are discussed.

Philadelphia-chromosome-negative chronic myelogenous leukemia with incomplete trisomy 1q following chemotherapy for ovarian carcinoma.

A 59-year-old woman was treated with surgery followed by monthly injections of the alkylating agent thiotepa for a granulosa cell tumor of the left ovary. Chemotherapy was continued for 22 years. At the age of 84, chronic myelogenous leukemia (CML) developed. Cytogenetic studies revealed incomplete trisomy of the long arm of chromosome No. 1 as the only karyotypic abnormality. No Philadelphia chromosome was detected. The significance of trisomy 1q as an isolated cytogenetic abnormality in CML and the occurrence of CML following treatment of ovarian cancer are discussed.